A Human Cellular Model for Studying the Regulation of Glucagon-Like Peptide-1 Secretion

GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released from L cells in the intestine. The regulation of GLP-1 secretion has been described both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signa...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2001-10, Vol.142 (10), p.4522-4528
Main Authors: Reimer, Raylene A, Darimont, Christian, Gremlich, Sandrine, Nicolas-Métral, Valérie, Rüegg, Urs T, Macé, Katherine
Format: Article
Language:English
Subjects:
Animal models
Animal species
Animals
Calcium (intracellular)
Carbachol
Cell culture
Cell differentiation
Cell Line
Cholinergics
Diet
Dose-Response Relationship, Drug
Gastrin
Gastrin-releasing peptide
Gene expression
Glucagon
Glucagon - secretion
Glucagon-Like Peptide 1
Humans
Hydrolysates
In vivo methods and tests
Intestine
Intestines - physiology
Ionomycin
L cells
Meat
Nutrients
Oleic acid
Oleic Acid - pharmacology
Palmitic acid
Palmitic Acid - pharmacology
Peptide Fragments - secretion
Peptides
Protein Hydrolysates - pharmacology
Protein Precursors - secretion
Secretion
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Summary:GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released from L cells in the intestine. The regulation of GLP-1 secretion has been described both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signaling pathways regulating GLP-1 secretion were investigated in the NCI-H716 human intestinal cell line. After differentiation, these cells homogeneously produced 16.8 pmol GLP-1/mg protein with a basal release of 4.2% during a 2-h incubation period. Nutrients, such as palmitic acid, oleic acid, and meat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neuromediator gastrin-releasing peptide. Along with stimulating GLP-1 release, gastrin-releasing peptide, like ionomycin, increased intracellular calcium levels. Activators of PKA and PKC were able to increase GLP-1 secretion in NCI-H716 cells. However, neither PKA activators nor meat hydrolysate increased proglucagon mRNA levels. These findings indicate that the NCI-H716 cell line constitutes a unique model to study the cellular mechanism of GLP-1 secretion in humans and suggest potential interspecies divergence in the regulation of proglucagon gene expression in enteroendocrine cells.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.142.10.8415